title: Randomized double-blind trial of sulindac and etodolac to eradicate aberrant crypt foci and to prevent sporadic colorectal polyps.
abstract: OBJECTIVE
  On the basis of the results of our preliminary trial suggesting that aberrant crypt foci (ACF) could be eradicated by short-term administration of sulindac, in the present study, we explored the feasibility of using ACF as surrogate markers for chemoprevention of colorectal cancer.
  
  
  METHODS
  Randomly assigned to sulindac (300 mg daily), etodolac (400 mg daily), and placebo groups were 189 subjects without polyps or who had undergone polypectomy. Drugs were administered for 2 months. ACF in the rectal region were counted by magnifying endoscopy. Occurrence of polyps was evaluated at 12 months. A planned interim analysis was conducted.
  
  
  RESULTS
  ACF number at 2 months was significantly suppressed in the sulindac group (P = 0.0075), but not in the etodolac group (P = 0.73). In the sulindac group, the numbers of adenomas plus hyperplastic polyps (total polyps) and adenomas at 12 months were significantly (P = 0.02) and marginally (P = 0.064) lower, respectively, in comparison with the placebo group; no such difference was observed in the etodolac group. In analysis of only polypectomized subjects, the numbers of total polyps and adenomas in the sulindac group were even more markedly lower, with P values of 0.014 and 0.034, respectively. A similar tendency was confirmed by analyses of the incidence of polyps at 12 months. Suppression rates of total polyps and adenomas in ACF responders to sulindac were significantly greater than in nonresponders. In all groups, compliance was more than 90% and no intolerable adverse effects were observed.
  
  
  CONCLUSIONS
  ACF may be useful as surrogate lesions for chemoprevention of colorectal cancer.
authors.affiliation: Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagashima
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Nojiri
authors.forename: Michiaki
authors.initials: M
authors.lastname: Hirayama
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nakano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sekikawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Mori
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sonoda
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kimura
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Niitsu
mesh_terms: D058739:Aberrant Crypt Foci / Q000188:drug therapy*; D000236:Adenoma / Q000188:drug therapy; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003111:Colonic Polyps / Q000473:pathology / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D017308:Etodolac / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013467:Sulindac / Q000627:therapeutic use*
chemical_list: D013467:Sulindac; D017308:Etodolac